ABSTRACT: Inflammatory genes serve a crucial role in the pathogenesis of in?ammation?associated tumors. However, as recent studies have mainly focused on the effects of single inflammatory genes on colorectal cancer (CRC), but not on the global interactions between genes, the underlying mechanisms between inflammatory genes and CRC remain unclear. In the current study, two inflammation?associated networks were constructed based on inflammatory genes, differentially expressed genes (DEGs) in CRC vs. normal samples, and protein?protein interactions (PPIs). These networks included an inflammation?related neighbor network (IRNN) and an inflammation?related DEG network (IRDN). Notably, the results indicated that the inflammatory genes served as important CRC?associated genes in the IRNN. Certain inflammatory genes were more likely to be network hubs and exhibited higher betweenness centralities, indicating that these inflammatory hub genes had central roles in the communication between genes in the IRNN. By contrast, in the IRDN, functional enrichment analysis revealed that genes were enriched in numerous cancer?associated functions and pathways. Subsequently, 14 genes in a module were identified in the IRDN as the potential biomarkers associated with disease?free survival (DFS) in CRC patients in the GSE24550 dataset, the prognosis of which was further validated using three independent datasets (GSE24549, GSE34551 and GSE103479). All 14 genes (including BCAR1, CRK, FYN, GRB2, LCP2, PIK3R1, PLCG1, PTK2, PTPN11, PTPN6, SHC1, SOS1, SRC and SYK) in this module were inflammatory genes, emphasizing the critical role of inflammation in CRC. In conclusion, these findings based on integrated inflammation?associated networks provided a novel insight that may help elucidate the inflammation?mediated mechanisms involved in CRC.
